1. CNTF+BDNF treatment and neuroprotective pathways in the rd1 mouse retina.
- Author
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Azadi S, Johnson LE, Paquet-Durand F, Perez MT, Zhang Y, Ekström PA, and van Veen T
- Subjects
- Animals, Apoptosis drug effects, Apoptosis physiology, Brain-Derived Neurotrophic Factor therapeutic use, Cell Survival drug effects, Cell Survival physiology, Ciliary Neurotrophic Factor therapeutic use, Cyclic AMP Response Element-Binding Protein drug effects, Cyclic AMP Response Element-Binding Protein metabolism, Disease Models, Animal, Down-Regulation drug effects, Down-Regulation physiology, Drug Therapy, Combination, Extracellular Signal-Regulated MAP Kinases drug effects, Extracellular Signal-Regulated MAP Kinases metabolism, Fibroblast Growth Factor 2 drug effects, Fibroblast Growth Factor 2 metabolism, Mice, Mice, Inbred C3H, Mice, Neurologic Mutants, Neuroprotective Agents therapeutic use, Organ Culture Techniques, Phosphorylation drug effects, Photoreceptor Cells drug effects, Photoreceptor Cells metabolism, Proto-Oncogene Proteins c-akt drug effects, Proto-Oncogene Proteins c-akt metabolism, Retina metabolism, Retinitis Pigmentosa metabolism, Retinitis Pigmentosa physiopathology, Signal Transduction physiology, Brain-Derived Neurotrophic Factor pharmacology, Ciliary Neurotrophic Factor pharmacology, Neuroprotective Agents pharmacology, Retina drug effects, Retinitis Pigmentosa drug therapy, Signal Transduction drug effects
- Abstract
The rd1 mouse is a relevant model for studying the mechanisms of photoreceptor degeneration in retinitis pigmentosa. Treatment with ciliary neurotrophic factor (CNTF) in combination with brain derived neurotrophic factor (BDNF) is known to rescue photoreceptors in cultured rd1 retinal explants. To shed light on the underlying mechanisms, we studied the effects of 9 days (starting at postnatal day 2) in vitro CNTF+BDNF treatment on the endogenous production of CNTF, BDNF, fibroblast growth factor 2 (FGF2), or the activation of extracellular signal-regulated kinase (ERK), Akt and cAMP-response-element-binding protein (CREB) in retinal explants. In rd1 explants, CNTF+BDNF decreased the number of TUNEL-positive photoreceptors. The treatment also increased endogenous rd1 levels of CNTF and BDNF, but lowered the level of FGF2 expression in rd1 explants. When wild-type explants were treated, endogenous CNTF was similarly increased, while BDNF and FGF2 levels remained unaffected. In addition, treatment of rd1 retinas strongly increased the phosphorylation of ERK, Akt and CREB. In treated wild-type explants, the same parameters were either unchanged (ERK) or decreased (Akt and CREB). The results suggest a role for Akt, ERK and CREB in conveying the neuroprotective effect of CNTF+BDNF treatment in rd1 retinal explants.
- Published
- 2007
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